Synthesis of 5,7-dinitroquinolines from 2,4,6-trinitrotoluene

Full text of DOI:10.1016/j.mencom.2007.06.018

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 234–236
Synthesis of 5,7-dinitroquinolines from 2,4,6-trinitrotoluene
Vasilii V. Mezhnev, Mikhail D. Dutov, Oleg Yu. Sapozhnikov,
Vadim V. Kachala and Svyatoslav A. Shevelev*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow,
Russian Federation. Fax: +7 495 135 5328; e-mail: Shevelev@ioc.ac.ru
DOI: 10.1016/j.mencom.2007.06.018
A method for synthesising hitherto unknown 5,7-dinitroquinolines has been developed.
This study aimed at the utilisation of an explosive, 1,3,5-tri-
nitrobenzene (TNB), as a key starting compound for the
synthesis of polyfunctional benzannelated heterocycles.1,2
Previously, benzannelated heteroaromatic systems were obtained
by modification of the methyl group in trinitrotoluene (TNT)
followed by cyclisation.2–10
It is well known that quinolines can be obtained by cyclo-
condensation of ortho-aminobenzaldehydes or ortho-amino-
anils with carbonyl compounds containing a reactive methylene
fragment.11
TNT can be readily converted to 2,4,6-trinitrobenzaldehyde
112 and N-(2,4,6-trinitrobenzylidene)anilines 2.6 To obtain
starting compounds for the synthesis of quinolines, we selec-
tively reduced an ortho-nitro group in aldehyde 1 or anil 2 to
the amino group.
fact, condensation of aldehyde 1 with 4-(N,N-dimethylamino)-
aniline (refluxing in benzene in the presence of p-toluene-
sulfonic acid) gave anil 3, which was completely different from
the condensation product of TNT with 4-nitroso-N,N-dimethyl-
aniline (1H NMR data and mp). Mass spectra provide little
information for establishing the structure of compound 4, since
the spectrum of 3 contains a molecular ion whereas that of 4
contains [M – 16]. Confirmation that compound 4 has a nitrone
structure was obtained by elemental analysis of the purified
individual product, which differed considerably from the elemental
analysis of anil 3 and was totally consistent with its N-oxide,
i.e., nitrone 4. It should be noted that the structure of the con-
densation product of TNT with 4-nitroso-N,N-dimethylaniline
was assigned previously without reliable proof.14,15 The acidic
hydrolysis of anil 3 to 2,4,6-trinitrobenzaldehyde 1, which is
used12 to synthesise 1, is in fact the hydrolysis of nitrone 4
(Scheme 1).
Ar
N
O
N
O2N
NO2
O2N
NO2
NO2
NO2
N
O
1
2
H2N
N
O2N
NO2
O2N
NO2
However, the direct selective reduction of o-NO2 in aldehyde
1 or anils 2 was found impossible: no matter what reducing
agent was used, complex product mixtures were always formed.
Another method could involve replacement of o-NO2 with
an azido group followed by reduction of the latter. However,
azidation is non-selective in the case of aldehyde 1: both o- and
p-NO2 are replaced on treatment with NaN3. It is known6 that
only o-NO2 is replaced in the azidation of anils 2, but they
concurrently undergo cyclisation to give 2-aryl-4,6-dinitro-
indazoles. Anil 3 (its N-oxide 4) is the only exception: treat-
ment of this compound with NaN3 results in a quite stable
2-azidoanil (Scheme 1). Note that anils 2 have been obtained by
condensation of aldehyde 1 with anilines,6 whereas anil 3, as it
was previously reported, was supposedly obtained by condensa-
tion of TNT with 4-nitroso-N,N-dimethylaniline (Scheme 1) in
pyridine in the presence of a catalytic amount of iodine.12
This considerable difference in the behaviour of the azide
based on anil 3 and azides based on other anils 2, as well as the
fact that the condensation product of 2,4-dinitrotoluene with
4-nitroso-N,N-dimethylaniline obtained under the same condi-
tions as anil 3 is not an anil but its N-oxide (nitrone), which has
been proved chemically,13 has suggested that anil 3 is in fact
nitrone 4 and its azidation product is nitrone 5 (Scheme 1). In
TsOH
NO2
NO2
1
3
ON
N
O2N
NO2
N
N
Py, I2
NO2
N
N
TNT
O
O2N
NO2
NaN3
DMF
O
O2N
NO2
N3
4
H2O / HCl
NO2
5
1
Scheme 1
– 234 –

Mendeleev Commun., 2007, 17, 234–236
Thus, of the above TNT derivatives, only 2-azidonitrone 5
could be a starting compound for the synthesis of quinolines,
provided that the N3 group could be reduced to NH2 without
affecting the nitro groups. It was found that selective reduction
of the N3 group in 2-azidonitrone 5 with standard reducing
agents failed, even if agents that reportedly reduce the N3 group
in the presence of an aromatic nitro group were used.16,17 The
selective N3 reduction in the presence of nitro groups was
performed previously18 in 2-azido-4,6-dinitrostilbenes 6: treat-
ment of stilbene 6 with cyclohexane-1,3-dione results in diazo
transfer (instead of aryl azide cycloaddition 1,3-diketone observed
usually) to give 2-amino-4,6-dinitrostilbenes 7 and 2-diazo-
cyclohexane-1,3-dione (Scheme 2).
N
N
N
N
O
O
O
O
+
N2
Et3N, DMSO,
~20 °C
O
O2N
O
O2N
N3
NH2
NO2
NO2
5
8
Scheme 3
Ar
Ar
The condensation of 2-aminonitrone 8 with 1,3-dicarbonyl
compounds in boiling acetic acid results in 5,7-dinitroquinoline
derivatives 9 in 25–35% yields (Scheme 4).‡
O
O
O
O
O2N
N3
O2N
NH2
The condensation direction in the case of non-symmetrical
1,3-dicarbonyl compounds was assigned by analogy with the
known syntheses of quinolines by condensation of ortho-amino-
aldehydes and ortho-aminoanils with 1,3-dicarbonyl compounds:
the more reactive carbonyl group undergoes condensation with
the amino group11 (in the examples we studied, the aliphatic
MeC=O group is much more reactive than the aromatic PhC=O
group and even more reactive than the carbonyl in the ester
group EtOC=O).
+
N2
NO2
NO2
6
7
Scheme 2
2-Azidonitrone 5 was smoothly converted into 4-(N,N-di-
methylamino)phenylimine N-oxide 8 (yield of above 80%) on
treatment with cyclohexane-1,3-dione (Scheme 3).†
NO2
O
O
O
N
†
The 1H NMR spectra were recorded with a Bruker AC-200 instrument.
R
R
+
8
Two-dimensional spectra were recorded in the gradient mode using a
Bruker DRX-500 instrument at frequencies of 500.13 and 125.26 MHz
for 1H and 13C, respectively. Chemical shifts (d) are reported relative to
TMS. Mass spectra were obtained using a Kratos MS-30 instrument; the
ionization energy was 70 eV. The melting points of the resulting com-
pounds were determined on a Boetius hot stage using Koffler’s technique
(the heating rate was 4 K min–1).
HO
AcOH; ∆
O2N
N
N
H
9
10
a R = Me
b R = Ph
c R = OEt
Scheme 4
N-(2,4,6-Trinitrobenzylidene)-4-(N',N'-dimethylamino)aniline 3. A solu-
tion of 2,4,6-trinitrobenzaldehyde (3 mmol) and N,N-dimethyl-p-phenylene-
diamine (3 mmol) in benzene (50 ml) was refluxed with a water separator
(Dean-Stark trap) in the presence of several TsOH crystals until the starting
compounds disappeared completely (5–6 h, TLC). The azomethine pre-
cipitate was filtered off and washed with benzene, then recrystallised
from DMF. Yield 68%; mp 218–219 °C. 1H NMR ([2H6]DMSO) d: 9.07
[s, 2H, C6H2(NO2)3], 8.85 (s, 1H, CH), 7.25 (d, 2H, C6H4), 6.80 (d, 2H,
C6H4), 2.99 (s, 6H, NMe2). Found (%): C, 50.39; H, 3.70; N, 19.60.
Calc. for C15H13N5O6 (%): C, 50.14; H, 3.65; N, 19.49.
N-(2,4,6-Trinitrobenzylidene)-4-(N',N'-dimethylamino)aniline N-oxide 4.12
Recrystallised from EtOH; mp > 250 °C. 1H NMR ([2H6]DMSO) d: 9.05
[s, 2H, C6H2(NO2)3], 8.91 (s, 1H, CH), 7.71 (d, 2H, C6H4), 6.80 (d, 2H,
C6H4), 3.02 (s, 6H, NMe2). Found (%): C, 48.09; H, 3.47; N, 18.71.
Calc. for C15H13N5O7 (%): C, 48.01; H, 3.49; N, 18.66.
‡
General procedure for the synthesis of 5,7-dinitroquinolines. A solu-
tion of compound 8 (3 mmol) and a corresponding 1,3-dicarbonyl com-
pound (6 mmol) was refluxed for 8 h in acetic acid (30 ml) (TLC). The
solution was concentrated to dryness. HCl (5% solution) was added, and
the mixture was extracted with chloroform. The organic layer was dried
with Na2SO4 and concentrated in vacuo. The residue was passed through
a column filter packed with silica gel. The resulting compound was
recrystallised from ethanol.
1-(2-Methyl-5,7-dinitroquinolin-3-yl)ethanone 9a. Yield 33%; mp 114–
115 °C. 1H NMR ([2H6]DMSO) d: 9.19 [s, 1H, C6H2(NO2)2], 9.04 [s,
1H, C6H2(NO2)2], 8.98 (s, 1H, C5NH), 2.83 (s, 3H, Me), 2.75 (s, 3H,
Me). Found (%): C, 52.38; H, 3.33; N, 15.30. Calc. for C12H9N3O5 (%):
C, 52.37; H, 3.30; N, 15.27.
1-(2-Methyl-5,7-dinitroquinolin-3-yl)(phenyl)methanone 9b. Yield 27%;
1
(2-Azido-4,6-dinitrobenzylidene)-4-(
N
',
N
'-dimethylamino)aniline
N-oxide
5.
mp 138–140 °C. H NMR ([2H6]acetone) d: 9.19 [s, 1H, C6H2(NO2)2],
NaN3 (10 mmol) was added with stirring to a solution of 4 (10 mmol) in
DMF (20 ml). The stirring of the solution was continued for another 6 h
(TLC) at room temperature. The reaction mixture was poured onto ice.
The precipitate was filtered off and recrystallised from acetonitrile. Yield
85%; mp 175 °C (decomp.). 1H NMR ([2H6]DMSO) d: 8.52 [s, 1H,
C6H2(NO2)2], 8.44 [d, 2H, C6H2(NO2)2 + CHN], 7.72 (d, 2H, C6H4),
6.75 (d, 2H, C6H4), 3.02 (s, 6H, NMe2). Found (%): C, 48.50; H, 3.55;
N, 26.38. Calc. for C15H13N7O5 (%): C, 48.52; H, 3.53; N, 26.41.
9.10 [s, 1H, C6H2(NO2)2], 9.02 (s, 1H, C5NH), 7.95 (d, 2H, Ph), 7.77 (t,
1H, Ph), 7.62 (t, 2H, Ph), 2.75 (s, 3H, Me). Found (%): C, 60.55; H, 3.31;
N, 12.49. Calc. for C17H11N3O5 (%): C, 60.54; H, 3.29; N, 12.46.
Ethyl 2-methyl-5,7-dinitroquinoline-3-carboxylate 9c. Yield 25%;
mp 168–170 °C. 1H NMR ([2H6]DMSO) d: 9.31 [s, 1H, C6H2(NO2)2],
9.08 [s, 1H, C6H2(NO2)2], 9.00 (s, 1H, C5NH), 4.48 (q, 2H, CH2), 2.95
(s, 3H, Me), 1.41 (t, 3H, Me). Found (%): C, 51.18; H, 3.62; N, 13.75.
Calc. for C13H11N3O6 (%): C, 51.15; H, 3.63; N, 13.77.
(
2-Amino-4,6-dinitrobenzylidene)-4-(
N
',
N
'-dimethylamino)aniline
N
-oxide
8
.
1-[2-Methyl-7-nitro-5-(thiophenyl)quinolin-3-yl]ethanone 11. Thio-
phenol (3 mmol) and K2CO3 (3 mmol) were added to a solution of
5,7-dinitroquinoline 9a (3 mmol) in N-MP (8 ml) with stirring. The
stirring of the solution was continued for another 6 h (TLC) at room
temperature. The reaction mixture was poured onto ice. The precipitate
was filtered off and recrystallised from ethanol. Yield 63%; mp 163–
Triethylamine (1.5 mmol) was added to a solution of azide 5 (3 mmol)
and cyclohexane-1,3-dione (3 mmol) in DMSO (8 ml) with stirring. The
stirring of the solution was continued for another 5 to 6 h (TLC) at room
temperature. The reaction mixture was poured onto ice. The precipitate
was filtered off and washed with chloroform (2×5 ml). Yield 81%;
mp > 350 °C. 1H NMR ([2H6]DMSO) d: 8.57 [s, 1H, C6H2(NO2)2], 7.94
[s, 1H, C6H2(NO2)2], 7.84 (s, 1H, CH), 7.78 (d, 2H, C6H4), 6.79 (d, 2H,
C6H4), 6.71 (s, 2H, NH2), 3.02 (s, 6H, NMe2). Found (%): C, 51.79; H,
4.63; N, 20.57. Calc. for C15H15N5O5 (%): C, 52.17; H, 4.38; N, 20.28.
1
165 °C. H NMR ([2H6]DMSO) d: 8.96 [s, 1H, C6H2NO2], 8.62 [s, 1H,
C6H2(NO2)], 8.00 (s, 1H, C5NH), 7.60–7.46 (m, 5H, Ph), 2.81 (s, 3H,
Me), 2.69 (s, 3H, Me). Found (%): C, 63.86; H, 4.16; N, 8.30. Calc. for
C18H14N2O3S (%): C, 63.89; H, 4.17; N, 8.28.
– 235 –

Mendeleev Commun., 2007, 17, 234–236
Furthermore, the structure of compound 9b was established
References
based on HSQC and HMBC spectral data: the HMBC spectrum
contained cross-peaks between the methyl group protons and
the C-2 and C-3 atoms of the quinoline ring (but there were no
cross-peaks between the methyl group protons and C-4), as
well as between H-4 and the carbonyl carbon atom. These data
show unambiguously that the methyl group is located at C-2,
whereas the benzoyl group is located at C-3.
All carbons and protons were discovered in 1D spectra by
HSCQ and HMBC: HSQC showed one-bond H-C correlations
thus all non-quarternary carbon atoms were discovered. Benzoyl
group at C-3 was revealed using 3-bond correlations between
H-4 and the carbonyl carbon atom, as well as between ortho
protons of a phenyl ring and this carbonyl atom. Because there
is no other position of substitution of a quinoline ring leading to
these results, it is clear that benzoyl is placed at C-3.
The low yields of 5,7-dinitroquinolines 9 may be due to the
ability of the second reaction product, N-substituted hydroxyl-
amine 10 (Scheme 4), to react with both the starting reagents
and the products (reduction, condensation etc.). As far as we
are aware, there are no reported examples of the formation of
quinolines in condensation of ortho-aminoanil N-oxides with
carbonyl compounds.
It is known that for 4,6-dinitro-substituted five-membered
aromatic benzannelated heterocycles obtained from TNT, treat-
ment of them with anionic O-, S- and N-nucleophiles results
in regioselective replacement of 4-NO2, i.e., the nitro group
adjacent to the heterocyclic frame.9,10,12,19–22 We have shown
for the reaction of 5,7-dinitroquinoline 9a with thiophenol in
the presence of K2CO3 (in N-MP) that, in the case of the six-
membered dinitro-substituted benzannelated aromatic heterocycle,
again only the nitro group, which is most proximate to the hetero-
cyclic frame, i.e., 5-NO2, is replaced selectively (Scheme 5).‡
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8
9
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NO2
O
S
O
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PhSH
K2CO3, N-MP,
~20 °C
O2N
N
O2N
N
9a
11
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Scheme 5
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The structure of compound 11 was determined using two-
dimensional NOESY NMR spectra. The NOESY spectrum
contained intense cross-peaks between the H6 and H4 protons
of the quinoline ring and the ortho protons of the phenyl
substituent (H-2'), whereas signals between the H-8 and H-2'
were absent, which is only possible if the nitro group at the
5-position is replaced.
Received: 28th December 2006; Com. 06/2854
– 236 –